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目的:观察记录顺铂作用下急性分离新生大鼠耳蜗螺旋神经节细胞(SGNs)延迟整流钾通道的电流曲线,分析顺铂对SGNs钾电流激活动力学的影响,并初步探讨其耳毒性机制。方法:采用全细胞膜片钳技术记录SGNs外向延迟整流钾电流及顺铂对此电流的影响。结果:钳制电压为-60mV,刺激电压从-60mV到+80mV逐渐去极化,阶跃电压为10mV,持续时间为500ms,可在SGNs上记录到外向钾电流,该电流对TEA-Cl(4-乙基胺)敏感,具有延迟整流特性;在细胞外液中加入10μmol/L顺铂,能明显抑制SGNs延迟整流钾电流;顺铂对此电流的抑制作用与细胞外液中顺铂的浓度呈剂量依赖性;外液洗脱后SGNs电流可基本恢复正常。结论:钾通道与SGNs动作电位的产生密切相关,顺铂可抑制SGNs钾通道电流,导致听觉功能障碍。
OBJECTIVE: To observe the current curve of delayed rectifier potassium channel in acutely isolated cochlear spiral ganglion cells (SGNs) of neonatal rats with cisplatin, and to investigate the effect of cisplatin on the kinetics of potassium current activation in SGNs and its mechanism of ototoxicity. Methods: Whole-cell patch-clamp technique was used to record the outward delayed rectifier potassium current and the effect of cisplatin on SGNs current. RESULTS: The clamp voltage was -60 mV, the stimulus voltage gradually depolarized from -60 mV to +80 mV, the step voltage was 10 mV and the duration was 500 ms. Outward potassium current was recorded on SGNs, - ethylamine) with delayed rectification. The addition of 10μmol / L cisplatin to the extracellular fluid significantly inhibited the delayed rectifier potassium currents in SGNs. The inhibitory effect of cisplatin on this current was not related to the concentration of cisplatin in extracellular fluid In a dose-dependent manner; the SGNs current returned to normal after external elution. CONCLUSION: Potassium channel is closely related to the action potentials of SGNs. Cisplatin can inhibit the current of potassium channel in SGNs, resulting in auditory dysfunction.